Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
Nephrol Dial Transplant. 2020 Feb 1;35(2):291-297. doi: 10.1093/ndt/gfy314.
In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD.
The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD.
In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P < 0.001; 0.82 (0.71-0.94), P = 0.005, respectively}. In the longitudinal cohort, the uEGF:MCP-1 ratio correlated more closely with the percentage change of eGFR slope (r = 0.33, P < 0.001) as compared with uEGF/Cr or uMCP-1/Cr alone. The composite endpoint was defined as end-stage renal disease or 30% reduction of eGFR. These three markers were independently associated with composite endpoint after adjusting for potential confounders [hazard ratio 0.76 (0.59-1.00), P = 0.047 for uEGF/Cr; 1.18 (1.02-1.38), P = 0.028 for uMCP-1/Cr; 0.79 (0.68-0.91), P = 0.001 for uEGF/MCP-1].
In Chinese patients, urinary EGF/MCP-1 was negatively associated with the occurrence of DKD. Moreover, uEGF/MCP-1 had a better ability to predict the composite endpoint and correlated more closely with kidney function decline in advanced DKD as compared with uEGF/Cr or uMCP-1/Cr alone.
在糖尿病肾病（DKD）中，寻找预测疾病发生和进展的生物标志物很重要。除了肾小球损伤外，肾小管损伤和炎症也参与了 DKD 的发展。本研究探讨了尿表皮生长因子（uEGF）、单核细胞趋化蛋白-1（MCP-1）和 uEGF:MCP-1 比值与早期和晚期 DKD 患者肾脏受累的关系。
在中国的两项基于人群的研究中测量了 uEGF 和 uMCP-1 的浓度。在一项横断面研究（n=1811）中，研究了 uEGF、uMCP-1 和 uEGF/MCP-1 与 DKD 发生的关系，该研究纳入了早期 DKD 患者。在一项晚期 DKD 的纵向队列研究（n=208）中，评估了基线 uEGF、uMCP-1 和 uEGF/MCP-1 与肾脏结局的关系。
在两项研究中，uEGF/尿肌酐（Cr）与采样时估计肾小球滤过率（eGFR）之间以及 uMCP-1/Cr 与尿白蛋白:肌酐比值（uACR）之间均呈正相关。在横断面研究中，uEGF/Cr 和 uEGF/MCP-1 与 DKD 的发生呈负相关{比值比（OR）0.65 [95%置信区间（CI）0.54-0.79]，P<0.001；0.82（0.71-0.94），P=0.005}。在纵向队列中，uEGF:MCP-1 比值与 eGFR 斜率的变化百分比相关性更密切（r=0.33，P<0.001），而与 uEGF/Cr 或 uMCP-1/Cr 单独相比。复合终点定义为终末期肾病或 eGFR 降低 30%。在调整潜在混杂因素后，这三个标志物与复合终点独立相关[uEGF/Cr 的危险比 0.76（0.59-1.00），P=0.047；uMCP-1/Cr 的 1.18（1.02-1.38），P=0.028；uEGF/MCP-1 的 0.79（0.68-0.91），P=0.001]。
在中国患者中，尿 EGF/MCP-1 与 DKD 的发生呈负相关。此外，与 uEGF/Cr 或 uMCP-1/Cr 单独相比，uEGF/MCP-1 能够更好地预测复合终点，并与晚期 DKD 患者的肾功能下降相关性更密切。
